全文获取类型
收费全文 | 98篇 |
免费 | 6篇 |
专业分类
104篇 |
出版年
2021年 | 1篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 4篇 |
2014年 | 8篇 |
2013年 | 4篇 |
2012年 | 3篇 |
2011年 | 3篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1987年 | 1篇 |
1977年 | 2篇 |
1962年 | 1篇 |
1955年 | 1篇 |
1952年 | 1篇 |
1948年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有104条查询结果,搜索用时 0 毫秒
71.
NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta 总被引:4,自引:0,他引:4
Greten FR Arkan MC Bollrath J Hsu LC Goode J Miething C Göktuna SI Neuenhahn M Fierer J Paxian S Van Rooijen N Xu Y O'Cain T Jaffee BB Busch DH Duyster J Schmid RM Eckmann L Karin M 《Cell》2007,130(5):918-931
IKKbeta-dependent NF-kappaB activation plays a key role in innate immunity and inflammation, and inhibition of IKKbeta has been considered as a likely anti-inflammatory therapy. Surprisingly, however, mice with a targeted IKKbeta deletion in myeloid cells are more susceptible to endotoxin-induced shock than control mice. Increased endotoxin susceptibility is associated with elevated plasma IL-1beta as a result of increased pro-IL-1beta processing, which was also seen upon bacterial infection. In macrophages enhanced pro-IL-1beta processing depends on caspase-1, whose activation is inhibited by NF-kappaB-dependent gene products. In neutrophils, however, IL-1beta secretion is caspase-1 independent and depends on serine proteases, whose activity is also inhibited by NF-kappaB gene products. Prolonged pharmacologic inhibition of IKKbeta also augments IL-1beta secretion upon endotoxin challenge. These results unravel an unanticipated role for IKKbeta-dependent NF-kappaB signaling in the negative control of IL-1beta production and highlight potential complications of long-term IKKbeta inhibition. 相似文献
72.
We report a novel staining technique for human brain slices that distinguishes clearly gray from white matter. Previously described techniques using either Prussian blue (Berlin blue) or phthalocyanine dyes usually have included a hot phenol pretreatment to prevent white matter staining. The technique we describe here does not require hot phenol pretreatment and allows the use of brains stored for postmortem periods of one to two years prior to staining. Our technique involves staining with copper(II) phthalocyanine-tetrasulfonic acid tetrasodium salt 1% in water for 2 h followed by acetic acid treatment; this produces excellent blue staining of gray matter with little white matter staining. The stained brain slices are excellent for teaching human brain anatomy and/or pathology, or for research purposes. 相似文献
73.
Marlies Cortés María J Fernández‐Aceñero MC Martínez‐Campanario Anna Esteve‐Codina Douglas S Darling Balázs Győrffy Toby Lawrence Douglas C Dean Antonio Postigo 《The EMBO journal》2017,36(22):3336-3355
Accumulation of tumor‐associated macrophages (TAMs) associates with malignant progression in cancer. However, the mechanisms that drive the pro‐tumor functions of TAMs are not fully understood. ZEB1 is best known for driving an epithelial‐to‐mesenchymal transition (EMT) in cancer cells to promote tumor progression. However, a role for ZEB1 in macrophages and TAMs has not been studied. Here we describe that TAMs require ZEB1 for their tumor‐promoting and chemotherapy resistance functions in a mouse model of ovarian cancer. Only TAMs that expressed full levels of Zeb1 accelerated tumor growth. Mechanistically, ZEB1 expression in TAMs induced their polarization toward an F4/80low pro‐tumor phenotype, including direct activation of Ccr2. In turn, expression of ZEB1 by TAMs induced Ccl2, Cd74, and a mesenchymal/stem‐like phenotype in cancer cells. In human ovarian carcinomas, TAM infiltration and CCR2 expression correlated with ZEB1 in tumor cells, where along with CCL2 and CD74 determined poorer prognosis. Importantly, ZEB1 in TAMs was a factor of poorer survival in human ovarian carcinomas. These data establish ZEB1 as a key factor in the tumor microenvironment and for maintaining TAMs’ tumor‐promoting functions. 相似文献
74.
Amino acid sequence versus morphological data and the interordinal relationships of mammals 总被引:2,自引:0,他引:2
To a large extent, the mutual affinities of the mammalian orders continue
to puzzle systematists, even though comparative anatomy and amino acid
sequencing offer a massive data base from which these relationships could
potentially be adduced. In the present paper the consistency index--the
number of character states less the number of characters in a data set,
divided by the total number of changes in the character states on a
cladogram--was used to examine the relative resolving powers of recently
published morphological and molecular- sequence data. Consistency indices
were calculated for previously published alpha crystallin A chain and
myoglobin amino acid-sequence cladograms and for four original amino
acid-sequence cladograms (alpha crystallin A, myoglobin, and alpha and beta
hemoglobin); these were found to be comparable to the consistency indices
of morphologically based cladograms. Qualitative comparisons between the
morphologically based and molecularly based trees were also made; only
moderate congruence between the two was observed. Moreover, there was a
general lack of congruence between the cladograms specified by each of the
four proteins. Amino acid-sequence and morphological data agreed on the
placement of edentates as an early eutherian offshoot and on the grouping
of hyracoids, proboscideans, and sirenians. Otherwise there was only
limited congruence: morphology strongly supported the grouping of
lagomorphs and rodents and the alliance of pholidotes and edentates, but
sequence analyses did not. The placement of tubulidentates differed widely
among proteins. Morphology indicated the close association of sirenians
with proboscideans; proteins suggested a pairing of sirenians with
hyracoids. Sequence data did not identify many (morphologically
well-diagnosed) orders as monophyletic (e.g., Lagomorpha).(ABSTRACT
TRUNCATED AT 250 WORDS)
相似文献
75.
Keld Poulsen Justyna MC Bahl Anja H Simonsen Steen G Hasselbalch Niels HH Heegaard 《Clinical proteomics》2014,11(1):12
Background
Transthyretin (TTR), an abundant protein in cerebrospinal fluid (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR isoforms. These isoforms may reflect conditions in vivo. Since increased oxidative stress has been linked to neurodegenerative disorders such as Alzheimer’s disease (AD) it is of interest to characterize CSF-TTR isoform distribution in AD patients and controls. Here, TTR isoforms are profiled directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76 samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17)), and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC, n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S-cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the total TTR protein. Results were correlated with diagnostic information and with levels of CSF AD biomarkers tau, phosphorylated tau, and amyloid β1-42 peptide.Results
Preliminary data highlighted the high risk of artifactual TTR modification due to ex vivo oxidation and thus the samples for this study were all collected using strict and uniform guidelines. The results show that TTR is significantly more modified on Cys(10) in the AD and MCI groups than in controls (NPH and HC) (p ≤ 0.0012). Furthermore, the NPH group, while having normal TTR isoform distribution, had significantly decreased amyloid β peptide but normal tau values. No obvious correlations between levels of routine CSF biomarkers for AD and the degree of TTR modification were found.Conclusions
AD and MCI patients display a significantly higher fraction of oxidatively modified TTR in CSF than the control groups of NPH patients and HC. Quantitation of CSF-TTR isoforms thus may provide diagnostic information in patients with dementia symptoms but this should be explored in larger studies including prospective studies of MCI patients. The development of methods for simple, robust, and reproducible inhibition of in vitro oxidation during CSF sampling and sample handling is highly warranted. In addition to the diagnostic information the possibility of using TTR as a CSF oxymeter is of potential value in studies monitoring disease activity and developing new drugs for neurodegenerative diseases. 相似文献76.
Lt. Col. Joseph F. Metzger MC USA Alice Kase B.S. Chauncey W. Smith USAF MSC 《Mycopathologia》1962,17(4):335-344
Summary A method is presented for the preparation of immune sera and detection by immunofluorescence ofC. immitis, S. schenckii, B. dermatitidis, C. neoformans, andC. albicans in surgical and autopsy material. Formalin fixation does not affect the antigens of the mycotic agents. There are no cross reactions except withC. immitis andC. neoformans, which can be differentiated by the site of the specific fluorescence in each organism. 相似文献
77.
The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC. 相似文献
78.
Church LD Filer AD Hidalgo E Howlett KA Thomas AM Rapecki S Scheel-Toellner D Buckley CD Raza K 《Arthritis research & therapy》2010,12(5):R184
Introduction
Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. 相似文献79.
Parturition and retention of fetal membranes were induced with PGF2α in 3 primiparous dairy cows. Starting on day 12 post partum (PP) the cows were treated with 500 μ g i.m. of ACTH-analogue (tetracosactid) every 6 h for 6 times. Changes in plasma concentrations of cortisol, progesterone and 15-ketodihydro-PGF2α were evaluated immediately after treatment. The effects on the resumption of ovarian activity were evaluated by clinical and ultrasound examinations and by progesterone and 15-ketodihydro-PGF2α analyses for 56 days after parturition. Treatment was able to induce a statistically significant (p < 0.01) similar increase in cortisol and progesterone after both the 1st and the 6th injections, in all cows. No changes in 15-ketodihydro-PGF2αconcentrations were seen after any of the injections of ACTH-analogue. The first corpus luteum (CL) was seen on day 18 PP (cow A), and 28 (cow B) and in both cases it was followed by a normal ovarian cyclicity. No CL was observed during the whole period of study in cow C. Progesterone profiles confirmed these clinical and ultrasonographic findings. The steroid output, especially progesterone, induced by the ACTH-analogue might be a stimulus for the onset of ovarian cyclicity, since 2 of the 3 animals ovulated earlier than expected. These findings point to the fact that interference with the stress system might have a positive effect on ovarian cyclicity. The different pattern of response does however demand further studies. 相似文献
80.
MC Chiale D Montalti MA Flamini P Fernández E Gimeno CG Barbeito 《Biotechnic & histochemistry》2016,91(1):30-37
The uropygial glands of birds are sebaceous organs that contribute to the water-repellent properties of the feather coat. We studied the histological and histochemical characteristics of the uropygial gland of chimango caracara using hematoxylin and eosin (H & E), Gomori´s trichrome, orcein, Gomori´s reticulin, periodic acid-Schiff (PAS), Alcian blue (AB) and a variety of lectins. The gland is composed of two lobes and a papilla with 20 downy feathers. It is surrounded by a capsule of dense connective tissue that contains elastic, reticular and smooth muscle fibers. The papilla is delicate and has two excretory ducts. The gland mass relative to body mass was 0.143%. Both adenomer cells and their secretions were stained with Sudan IV, PAS and AB, and were positive for numerous lectins that indicated the presence of lipids and carbohydrates. Immunohistochemical techniques to detect PCNA confirmed cell proliferation in the basal stratum of the adenomer cells. The lipids and glycoconjugates secreted by the uropygial gland serve numerous functions including protection against microorganisms. 相似文献